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| | ==Architecture of the Mediator Head module== | | ==Architecture of the Mediator Head module== |
| - | <StructureSection load='3rj1' size='340' side='right' caption='[[3rj1]], [[Resolution|resolution]] 4.30Å' scene=''> | + | <StructureSection load='3rj1' size='340' side='right'caption='[[3rj1]], [[Resolution|resolution]] 4.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3rj1]] is a 21 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RJ1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RJ1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3rj1]] is a 21 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RJ1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SE:SELENIUM+ATOM'>SE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SE:SELENIUM+ATOM'>SE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hzs|2hzs]], [[2hzm|2hzm]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3rj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rj1 OCA], [https://pdbe.org/3rj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rj1 RCSB], [https://www.ebi.ac.uk/pdbsum/3rj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rj1 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MED11, YMR112C, YM9718.11C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), SRB4, MED17, YER022W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), MED8, YBR193C, YBR1403 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), SRB6, MED22, YBR253W, YBR1721 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), SRB5, MED18, YGR104C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), SRB2, HRS2, MED20, YHR041C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), MED6, MTR32, YHR058C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rj1 OCA], [http://pdbe.org/3rj1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rj1 RCSB], [http://www.ebi.ac.uk/pdbsum/3rj1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rj1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MED20_YEAST MED20_YEAST]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.<ref>PMID:16076843</ref> <ref>PMID:16109375</ref> <ref>PMID:16263706</ref> <ref>PMID:16885025</ref> [[http://www.uniprot.org/uniprot/MED8_YEAST MED8_YEAST]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. MED8 binds to the consensus sequence 5'-[AC][AG]GAAAT-3' in both the UAS of SUC2 and the DRS2 of HXK2.<ref>PMID:9918841</ref> <ref>PMID:10526178</ref> <ref>PMID:11555651</ref> <ref>PMID:16076843</ref> <ref>PMID:16263706</ref> <ref>PMID:16885025</ref> [[http://www.uniprot.org/uniprot/MED6_YEAST MED6_YEAST]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.<ref>PMID:16076843</ref> <ref>PMID:16263706</ref> <ref>PMID:16885025</ref> <ref>PMID:9234719</ref> <ref>PMID:9845373</ref> [[http://www.uniprot.org/uniprot/MED17_YEAST MED17_YEAST]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.<ref>PMID:11555651</ref> <ref>PMID:16076843</ref> <ref>PMID:16263706</ref> <ref>PMID:16885025</ref> <ref>PMID:9845373</ref> [[http://www.uniprot.org/uniprot/MED11_YEAST MED11_YEAST]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex (PIC) with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. The essential MED11/22 heterodimer specifically functions in promoting stable PIC formation.<ref>PMID:16076843</ref> <ref>PMID:16263706</ref> <ref>PMID:16885025</ref> <ref>PMID:18691966</ref> [[http://www.uniprot.org/uniprot/MED22_YEAST MED22_YEAST]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.<ref>PMID:16076843</ref> <ref>PMID:16263706</ref> <ref>PMID:16885025</ref> [[http://www.uniprot.org/uniprot/MED18_YEAST MED18_YEAST]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.<ref>PMID:9845373</ref> <ref>PMID:11555651</ref> <ref>PMID:16076843</ref> <ref>PMID:16109375</ref> <ref>PMID:16263706</ref> <ref>PMID:16885025</ref> | + | [https://www.uniprot.org/uniprot/MED17_YEAST MED17_YEAST] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.<ref>PMID:11555651</ref> <ref>PMID:16076843</ref> <ref>PMID:16263706</ref> <ref>PMID:16885025</ref> <ref>PMID:9845373</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | + | [[Category: Large Structures]] |
| - | [[Category: Asturias, F J]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Berger, I]] | + | [[Category: Asturias FJ]] |
| - | [[Category: Cai, G]] | + | [[Category: Berger I]] |
| - | [[Category: Calero, G]] | + | [[Category: Cai G]] |
| - | [[Category: Cardelli, F]] | + | [[Category: Calero G]] |
| - | [[Category: Erdjument-Bromage, H]] | + | [[Category: Cardelli F]] |
| - | [[Category: Imasaki, T]] | + | [[Category: Erdjument-Bromage H]] |
| - | [[Category: Kornberg, G L]] | + | [[Category: Imasaki T]] |
| - | [[Category: Kornberg, R D]] | + | [[Category: Kornberg GL]] |
| - | [[Category: Takagi, Y]] | + | [[Category: Kornberg RD]] |
| - | [[Category: Tempst, P]] | + | [[Category: Takagi Y]] |
| - | [[Category: Tsai, K L]] | + | [[Category: Tempst P]] |
| - | [[Category: Yamada, K]] | + | [[Category: Tsai KL]] |
| - | [[Category: Head module]]
| + | [[Category: Yamada K]] |
| - | [[Category: Helical bundle]]
| + | |
| - | [[Category: Med]]
| + | |
| - | [[Category: Mediator]]
| + | |
| - | [[Category: Mediator head]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Pol ii]]
| + | |
| - | [[Category: Regulator]]
| + | |
| - | [[Category: Rna polymeras ii]]
| + | |
| - | [[Category: Rna polymerase ii]]
| + | |
| - | [[Category: Rnap]]
| + | |
| - | [[Category: Tbp]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcriptional regulation]]
| + | |
| Structural highlights
Function
MED17_YEAST Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Mediator is a key regulator of eukaryotic transcription, connecting activators and repressors bound to regulatory DNA elements with RNA polymerase II (Pol II). In the yeast Saccharomyces cerevisiae, Mediator comprises 25 subunits with a total mass of more than one megadalton (refs 5, 6) and is organized into three modules, called head, middle/arm and tail. Our understanding of Mediator assembly and its role in regulating transcription has been impeded so far by limited structural information. Here we report the crystal structure of the essential Mediator head module (seven subunits, with a mass of 223 kilodaltons) at a resolution of 4.3 angstroms. Our structure reveals three distinct domains, with the integrity of the complex centred on a bundle of ten helices from five different head subunits. An intricate pattern of interactions within this helical bundle ensures the stable assembly of the head subunits and provides the binding sites for general transcription factors and Pol II. Our structural and functional data suggest that the head module juxtaposes transcription factor IIH and the carboxy-terminal domain of the largest subunit of Pol II, thereby facilitating phosphorylation of the carboxy-terminal domain of Pol II. Our results reveal architectural principles underlying the role of Mediator in the regulation of gene expression.
Architecture of the Mediator head module.,Imasaki T, Calero G, Cai G, Tsai KL, Yamada K, Cardelli F, Erdjument-Bromage H, Tempst P, Berger I, Kornberg GL, Asturias FJ, Kornberg RD, Takagi Y Nature. 2011 Jul 3;475(7355):240-3. doi: 10.1038/nature10162. PMID:21725323[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kang JS, Kim SH, Hwang MS, Han SJ, Lee YC, Kim YJ. The structural and functional organization of the yeast mediator complex. J Biol Chem. 2001 Nov 9;276(45):42003-10. Epub 2001 Sep 12. PMID:11555651 doi:http://dx.doi.org/10.1074/jbc.M105961200
- ↑ Nair D, Kim Y, Myers LC. Mediator and TFIIH govern carboxyl-terminal domain-dependent transcription in yeast extracts. J Biol Chem. 2005 Oct 7;280(40):33739-48. Epub 2005 Aug 2. PMID:16076843 doi:http://dx.doi.org/M506067200
- ↑ Takagi Y, Kornberg RD. Mediator as a general transcription factor. J Biol Chem. 2006 Jan 6;281(1):80-9. Epub 2005 Nov 1. PMID:16263706 doi:http://dx.doi.org/M508253200
- ↑ Takagi Y, Calero G, Komori H, Brown JA, Ehrensberger AH, Hudmon A, Asturias F, Kornberg RD. Head module control of mediator interactions. Mol Cell. 2006 Aug 4;23(3):355-64. PMID:16885025 doi:http://dx.doi.org/S1097-2765(06)00412-6
- ↑ Holstege FC, Jennings EG, Wyrick JJ, Lee TI, Hengartner CJ, Green MR, Golub TR, Lander ES, Young RA. Dissecting the regulatory circuitry of a eukaryotic genome. Cell. 1998 Nov 25;95(5):717-28. PMID:9845373
- ↑ Imasaki T, Calero G, Cai G, Tsai KL, Yamada K, Cardelli F, Erdjument-Bromage H, Tempst P, Berger I, Kornberg GL, Asturias FJ, Kornberg RD, Takagi Y. Architecture of the Mediator head module. Nature. 2011 Jul 3;475(7355):240-3. doi: 10.1038/nature10162. PMID:21725323 doi:10.1038/nature10162
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